ID FURIN_HUMAN Reviewed; 794 AA. AC P09958; Q14336; Q6LBS3; Q9UCZ5; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 2. DT 27-MAR-2024, entry version 258. DE RecName: Full=Furin {ECO:0000303|PubMed:7690548}; DE EC=3.4.21.75 {ECO:0000269|PubMed:11799113, ECO:0000269|PubMed:1629222, ECO:0000269|PubMed:1713771, ECO:0000269|PubMed:2251280, ECO:0000269|PubMed:25974265, ECO:0000269|PubMed:7592877, ECO:0000269|PubMed:7690548, ECO:0000269|PubMed:9130696}; DE AltName: Full=Dibasic-processing enzyme; DE AltName: Full=Paired basic amino acid residue-cleaving enzyme; DE Short=PACE; DE Flags: Precursor; GN Name=FURIN {ECO:0000303|PubMed:7690548, ECO:0000312|HGNC:HGNC:8568}; GN Synonyms=FUR {ECO:0000303|PubMed:2408021}, PACE, PCSK3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Blood; RX PubMed=2408021; DOI=10.1093/nar/18.3.664; RA van den Ouweland A.M.W., van Duijnhoven H.L.P., Keizer G.D., RA Dorssers L.C.J., van de Ven W.J.M.; RT "Structural homology between the human fur gene product and the subtilisin- RT like protease encoded by yeast KEX2."; RL Nucleic Acids Res. 18:664-664(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=2251280; DOI=10.1073/pnas.87.23.9378; RA Wise R.J., Barr P.J., Wong P.A., Kiefer M.C., Brake A.J., Kaufman R.J.; RT "Expression of a human proprotein processing enzyme: correct cleavage of RT the von Willebrand factor precursor at a paired basic amino acid site."; RL Proc. Natl. Acad. Sci. U.S.A. 87:9378-9382(1990). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE RP SPECIFICITY. RX PubMed=1713771; DOI=10.1089/dna.1991.10.319; RA Barr P.J., Mason O.B., Landsberg K.E., Wong P.A., Kiefer M.C., Brake A.J.; RT "cDNA and gene structure for a human subtilisin-like protease with cleavage RT specificity for paired basic amino acid residues."; RL DNA Cell Biol. 10:319-328(1991). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-280. RX PubMed=2674906; DOI=10.1093/nar/17.17.7101; RA Van den Ouweland A.M.W., van Groningen J.J.M., Roebrock A.J.M., RA Onnekink C., Van de Ven W.J.M.; RT "Nucleotide sequence analysis of the human fur gene."; RL Nucleic Acids Res. 17:7101-7102(1989). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 296-794. RX PubMed=3023061; DOI=10.1002/j.1460-2075.1986.tb04484.x; RA Roebroek A.J.M., Schalken J.A., Leunissen J.A.M., Onnekink C., RA Bloemers H.P.J., van de Ven W.J.M.; RT "Evolutionary conserved close linkage of the c-fes/fps proto-oncogene and RT genetic sequences encoding a receptor-like protein."; RL EMBO J. 5:2197-2202(1986). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 402-428, FUNCTION, AND CATALYTIC ACTIVITY. RC TISSUE=Colon carcinoma; RX PubMed=7690548; DOI=10.1006/bbrc.1993.2146; RA Takahashi S., Kasai K., Hatsuzawa K., Kitamura N., Misumi Y., Ikehara Y., RA Murakami K., Nakayama K.; RT "A mutation of furin causes the lack of precursor-processing activity in RT human colon carcinoma LoVo cells."; RL Biochem. Biophys. Res. Commun. 195:1019-1026(1993). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 527-553, FUNCTION, CATALYTIC ACTIVITY, AND RP VARIANT ARG-547. RC TISSUE=Colon carcinoma; RX PubMed=7592877; DOI=10.1074/jbc.270.44.26565; RA Takahashi S., Nakagawa T., Kasai K., Banno T., Duguay S.J., RA Van de Ven W.J.M., Murakami K., Nakayama K.; RT "A second mutant allele of furin in the processing-incompetent cell line, RT LoVo. Evidence for involvement of the homo B domain in autocatalytic RT activation."; RL J. Biol. Chem. 270:26565-26569(1995). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, AND PROTEOLYTIC PROCESSING. RX PubMed=1629222; DOI=10.1016/s0021-9258(19)49712-3; RA Leduc R., Molloy S.S., Thorne B.A., Thomas G.; RT "Activation of human furin precursor processing endoprotease occurs by an RT intramolecular autoproteolytic cleavage."; RL J. Biol. Chem. 267:14304-14308(1992). RN [10] RP FUNCTION (MICROBIAL INFECTION), CATALYTIC ACTIVITY, AND COFACTOR. RX PubMed=1644824; DOI=10.1016/s0021-9258(18)42016-9; RA Molloy S.S., Bresnahan P.A., Leppla S.H., Klimpel K.R., Thomas G.; RT "Human furin is a calcium-dependent serine endoprotease that recognizes the RT sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective RT antigen."; RL J. Biol. Chem. 267:16396-16402(1992). RN [11] RP FUNCTION (MICROBIAL INFECTION), AND CATALYTIC ACTIVITY. RX PubMed=1438214; DOI=10.1073/pnas.89.21.10277; RA Klimpel K.R., Molloy S.S., Thomas G., Leppla S.H.; RT "Anthrax toxin protective antigen is activated by a cell surface protease RT with the sequence specificity and catalytic properties of furin."; RL Proc. Natl. Acad. Sci. U.S.A. 89:10277-10281(1992). RN [12] RP FUNCTION (MICROBIAL INFECTION). RX PubMed=8253774; DOI=10.1016/s0021-9258(19)74337-3; RA Tsuneoka M., Nakayama K., Hatsuzawa K., Komada M., Kitamura N., Mekada E.; RT "Evidence for involvement of furin in cleavage and activation of diphtheria RT toxin."; RL J. Biol. Chem. 268:26461-26465(1993). RN [13] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=7737999; DOI=10.1074/jbc.270.18.10618; RA Dubois C.M., Laprise M.H., Blanchette F., Gentry L.E., Leduc R.; RT "Processing of transforming growth factor beta 1 precursor by human furin RT convertase."; RL J. Biol. Chem. 270:10618-10624(1995). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [15] RP FUNCTION (MICROBIAL INFECTION), AND CATALYTIC ACTIVITY. RX PubMed=31091448; DOI=10.1016/j.celrep.2019.04.063; RA Braun E., Hotter D., Koepke L., Zech F., Gross R., Sparrer K.M.J., RA Mueller J.A., Pfaller C.K., Heusinger E., Wombacher R., Sutter K., RA Dittmer U., Winkler M., Simmons G., Jakobsen M.R., Conzelmann K.K., RA Poehlmann S., Muench J., Fackler O.T., Kirchhoff F., Sauter D.; RT "Guanylate-binding proteins 2 and 5 exert broad antiviral activity by RT inhibiting furin-mediated processing of viral envelope proteins."; RL Cell Rep. 27:2092-2104(2019). RN [16] RP 3D-STRUCTURE MODELING OF CATALYTIC DOMAIN. RX PubMed=8020465; DOI=10.1111/j.1432-1033.1994.tb18864.x; RA Siezen R.J., Creemers J.W.M., van de Ven W.J.M.; RT "Homology modelling of the catalytic domain of human furin. A model for the RT eukaryotic subtilisin-like proprotein convertases."; RL Eur. J. Biochem. 222:255-266(1994). RN [17] RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-773 AND SER-775, MOTIF, AND RP MUTAGENESIS OF SER-773 AND SER-775. RX PubMed=8846780; DOI=10.1002/j.1460-2075.1995.tb00275.x; RA Jones B.G., Thomas L., Molloy S.S., Thulin C.D., Fry M.D., Walsh K.A., RA Thomas G.; RT "Intracellular trafficking of furin is modulated by the phosphorylation RT state of a casein kinase II site in its cytoplasmic tail."; RL EMBO J. 14:5869-5883(1995). RN [18] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, RP IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF ASP-153. RX PubMed=9130696; DOI=10.1093/emboj/16.7.1508; RA Anderson E.D., VanSlyke J.K., Thulin C.D., Jean F., Thomas G.; RT "Activation of the furin endoprotease is a multiple-step process: RT requirements for acidification and internal propeptide cleavage."; RL EMBO J. 16:1508-1518(1997). RN [19] RP SUBCELLULAR LOCATION. RX PubMed=9412467; DOI=10.1083/jcb.139.7.1719; RA Liu G., Thomas L., Warren R.A., Enns C.A., Cunningham C.C., Hartwig J.H., RA Thomas G.; RT "Cytoskeletal protein ABP-280 directs the intracellular trafficking of RT furin and modulates proprotein processing in the endocytic pathway."; RL J. Cell Biol. 139:1719-1733(1997). RN [20] RP INTERACTION WITH PACS1, AND SUBCELLULAR LOCATION. RX PubMed=11331585; DOI=10.1093/emboj/20.9.2191; RA Crump C.M., Xiang Y., Thomas L., Gu F., Austin C., Tooze S.A., Thomas G.; RT "PACS-1 binding to adaptors is required for acidic cluster motif-mediated RT protein traffic."; RL EMBO J. 20:2191-2201(2001). RN [21] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, RP AND MUTAGENESIS OF VAL-72; ARG-75 AND ASP-153. RX PubMed=11799113; DOI=10.1074/jbc.m108740200; RA Anderson E.D., Molloy S.S., Jean F., Fei H., Shimamura S., Thomas G.; RT "The ordered and compartment-specfific autoproteolytic removal of the furin RT intramolecular chaperone is required for enzyme activation."; RL J. Biol. Chem. 277:12879-12890(2002). RN [22] RP FUNCTION. RX PubMed=20489134; DOI=10.1373/clinchem.2010.143883; RA Semenov A.G., Tamm N.N., Seferian K.R., Postnikov A.B., Karpova N.S., RA Serebryanaya D.V., Koshkina E.V., Krasnoselsky M.I., Katrukha A.G.; RT "Processing of pro-B-type natriuretic peptide: furin and corin as candidate RT convertases."; RL Clin. Chem. 56:1166-1176(2010). RN [23] RP FUNCTION. RX PubMed=21763278; DOI=10.1016/j.bbrc.2011.06.192; RA Peng J., Jiang J., Wang W., Qi X., Sun X.L., Wu Q.; RT "Glycosylation and processing of pro-B-type natriuretic peptide in RT cardiomyocytes."; RL Biochem. Biophys. Res. Commun. 411:593-598(2011). RN [24] RP FUNCTION (MICROBIAL INFECTION). RX PubMed=27582320; DOI=10.1038/srep32371; RA Schulte T., Mikaelsson C., Beaussart A., Kikhney A., Deshmukh M., RA Wolniak S., Pathak A., Ebel C., Lofling J., Fogolari F., RA Henriques-Normark B., Dufrene Y.F., Svergun D., Nygren P.A., Achour A.; RT "The BR domain of PsrP interacts with extracellular DNA to promote RT bacterial aggregation; structural insights into pneumococcal biofilm RT formation."; RL Sci. Rep. 6:32371-32371(2016). RN [25] RP FUNCTION (MICROBIAL INFECTION), AND CATALYTIC ACTIVITY. RX PubMed=32703818; DOI=10.26508/lsa.202000786; RA Bestle D., Heindl M.R., Limburg H., Van Lam van T., Pilgram O., Moulton H., RA Stein D.A., Hardes K., Eickmann M., Dolnik O., Rohde C., Klenk H.D., RA Garten W., Steinmetzer T., Boettcher-Friebertshaeuser E.; RT "TMPRSS2 and furin are both essential for proteolytic activation of SARS- RT CoV-2 in human airway cells."; RL Life. Sci Alliance 3:1-14(2020). RN [26] RP FUNCTION (MICROBIAL INFECTION), ACTIVITY REGULATION, AND CATALYTIC RP ACTIVITY. RX PubMed=32362314; DOI=10.1016/j.molcel.2020.04.022; RA Hoffmann M., Kleine-Weber H., Poehlmann S.; RT "A multibasic cleavage site in the Spike protein of SARS-CoV-2 is essential RT for infection of human lung cells."; RL Mol. Cell 78:779-784(2020). RN [27] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH LAMP1; LAMP2 AND RP LAMP3. RX PubMed=32295904; DOI=10.1128/jvi.00050-20; RA Ueo A., Kubota M., Shirogane Y., Ohno S., Hashiguchi T., Yanagi Y.; RT "Lysosome-Associated Membrane Proteins Support the Furin-Mediated RT Processing of the Mumps Virus Fusion Protein."; RL J. Virol. 94:0-0(2020). RN [28] RP ACTIVITY REGULATION. RX PubMed=34699015; DOI=10.1007/s10719-021-10018-8; RA Zeng J., Meng Y., Chen S.Y., Zhao G., Wang L., Zhang E.X., Qiu H.; RT "Structural characteristics of Heparan sulfate required for the binding RT with the virus processing Enzyme Furin."; RL Glycoconj. J. 0:0-0(2021). RN [29] {ECO:0007744|PDB:4OMC, ECO:0007744|PDB:4OMD} RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 108-574 IN COMPLEX WITH CALCIUM RP AND INHIBITOR, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND RP DISULFIDE BONDS. RX PubMed=24666235; DOI=10.1021/cb500087x; RA Dahms S.O., Hardes K., Becker G.L., Steinmetzer T., Brandstetter H., RA Than M.E.; RT "X-ray structures of human furin in complex with competitive inhibitors."; RL ACS Chem. Biol. 9:1113-1118(2014). RN [30] {ECO:0007744|PDB:4RYD} RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 108-574 IN COMPLEX WITH CALCIUM RP AND INHIBITOR, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND RP DISULFIDE BONDS. RX PubMed=25974265; DOI=10.1002/cmdc.201500103; RA Hardes K., Becker G.L., Lu Y., Dahms S.O., Kohler S., Beyer W., Sandvig K., RA Yamamoto H., Lindberg I., Walz L., von Messling V., Than M.E., Garten W., RA Steinmetzer T.; RT "Novel Furin inhibitors with potent anti-infectious activity."; RL ChemMedChem 10:1218-1231(2015). RN [31] RP VARIANTS VAL-43; SER-146; GLN-298 AND VAL-636. RX PubMed=32867305; DOI=10.3390/genes11091010; RA Latini A., Agolini E., Novelli A., Borgiani P., Giannini R., Gravina P., RA Smarrazzo A., Dauri M., Andreoni M., Rogliani P., Bernardini S., RA Helmer-Citterich M., Biancolella M., Novelli G.; RT "COVID-19 and Genetic Variants of Protein Involved in the SARS-CoV-2 Entry RT into the Host Cells."; RL Genes (Basel) 11:0-0(2020). CC -!- FUNCTION: Ubiquitous endoprotease within constitutive secretory CC pathways capable of cleavage at the RX(K/R)R consensus motif CC (PubMed:11799113, PubMed:1629222, PubMed:1713771, PubMed:2251280, CC PubMed:24666235, PubMed:25974265, PubMed:7592877, PubMed:7690548, CC PubMed:9130696). Mediates processing of TGFB1, an essential step in CC TGF-beta-1 activation (PubMed:7737999). Converts through proteolytic CC cleavage the non-functional Brain natriuretic factor prohormone into CC its active hormone BNP(1-32) (PubMed:20489134, PubMed:21763278). By CC mediating processing of accessory subunit ATP6AP1/Ac45 of the V-ATPase, CC regulates the acidification of dense-core secretory granules in islets CC of Langerhans cells (By similarity). {ECO:0000250|UniProtKB:P23188, CC ECO:0000269|PubMed:11799113, ECO:0000269|PubMed:1629222, CC ECO:0000269|PubMed:1713771, ECO:0000269|PubMed:20489134, CC ECO:0000269|PubMed:21763278, ECO:0000269|PubMed:2251280, CC ECO:0000269|PubMed:24666235, ECO:0000269|PubMed:25974265, CC ECO:0000269|PubMed:7592877, ECO:0000269|PubMed:7690548, CC ECO:0000269|PubMed:7737999, ECO:0000269|PubMed:9130696}. CC -!- FUNCTION: (Microbial infection) Cleaves and activates diphtheria toxin CC DT. {ECO:0000269|PubMed:8253774}. CC -!- FUNCTION: (Microbial infection) Cleaves and activates anthrax toxin CC protective antigen (PA). {ECO:0000269|PubMed:1438214, CC ECO:0000269|PubMed:1644824}. CC -!- FUNCTION: (Microbial infection) Cleaves and activates HIV-1 virus CC Envelope glycoprotein gp160. {ECO:0000269|PubMed:31091448}. CC -!- FUNCTION: (Microbial infection) Required for H7N1 and H5N1 influenza CC virus infection probably by cleaving hemagglutinin. CC {ECO:0000269|PubMed:25974265}. CC -!- FUNCTION: (Microbial infection) Able to cleave S.pneumoniae serine-rich CC repeat protein PsrP. {ECO:0000269|PubMed:27582320}. CC -!- FUNCTION: (Microbial infection) Facilitates human coronaviruses EMC and CC SARS-CoV-2 infections by proteolytically cleaving the spike protein at CC the monobasic S1/S2 cleavage site. This cleavage is essential for spike CC protein-mediated cell-cell fusion and entry into human lung cells. CC {ECO:0000269|PubMed:32362314, ECO:0000269|PubMed:32703818}. CC -!- FUNCTION: (Microbial infection) Facilitates mumps virus infection by CC proteolytically cleaving the viral fusion protein F. CC {ECO:0000269|PubMed:32295904}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Release of mature proteins from their proproteins by cleavage CC of -Arg-Xaa-Yaa-Arg-|-Zaa- bonds, where Xaa can be any amino acid and CC Yaa is Arg or Lys. Releases albumin, complement component C3 and von CC Willebrand factor from their respective precursors.; EC=3.4.21.75; CC Evidence={ECO:0000269|PubMed:11799113, ECO:0000269|PubMed:1438214, CC ECO:0000269|PubMed:1629222, ECO:0000269|PubMed:1644824, CC ECO:0000269|PubMed:1713771, ECO:0000269|PubMed:2251280, CC ECO:0000269|PubMed:24666235, ECO:0000269|PubMed:25974265, CC ECO:0000269|PubMed:31091448, ECO:0000269|PubMed:32362314, CC ECO:0000269|PubMed:32703818, ECO:0000269|PubMed:7592877, CC ECO:0000269|PubMed:7690548, ECO:0000269|PubMed:7737999, CC ECO:0000269|PubMed:8253774, ECO:0000269|PubMed:9130696}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:1644824, ECO:0000269|PubMed:24666235, CC ECO:0000269|PubMed:25974265, ECO:0000269|PubMed:9130696}; CC Note=Binds 3 calcium ions per subunit. {ECO:0000269|PubMed:24666235, CC ECO:0000269|PubMed:25974265, ECO:0000269|PubMed:9130696}; CC -!- ACTIVITY REGULATION: Inhibited by the not secondly cleaved propeptide CC (PubMed:9130696, PubMed:11799113). Inhibited by m-guanidinomethyl- CC phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine (m-guanidinomethyl- CC Phac-RVR-Amb) and 4-guanidinomethyl-phenylacetyl-Arg-Tle-Arg-4- CC amidinobenzylamide (MI-1148) (PubMed:24666235, PubMed:25974265). CC Inhibited by Decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decanoyl- CC RVKR-CMK) (PubMed:32362314). Inhibited by heparin/heparan sulfate- CC binding (PubMed:2408021). {ECO:0000269|PubMed:11799113, CC ECO:0000269|PubMed:2408021, ECO:0000269|PubMed:24666235, CC ECO:0000269|PubMed:25974265, ECO:0000269|PubMed:32362314, CC ECO:0000269|PubMed:9130696}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 6.0. {ECO:0000269|PubMed:9130696}; CC -!- SUBUNIT: Interacts with FLNA (By similarity). Binds to PACS1 which CC mediates TGN localization and connection to clathrin adapters CC (PubMed:11331585). Interacts with LAMP1, LAMP2 and LAMP3 CC (PubMed:32295904). {ECO:0000250|UniProtKB:P23188, CC ECO:0000269|PubMed:11331585, ECO:0000269|PubMed:32295904}. CC -!- INTERACTION: CC P09958; P05067: APP; NbExp=3; IntAct=EBI-1056807, EBI-77613; CC P09958; P50281: MMP14; NbExp=3; IntAct=EBI-1056807, EBI-992788; CC P09958; Q9H239: MMP28; NbExp=3; IntAct=EBI-1056807, EBI-20858485; CC P09958; O14793: MSTN; NbExp=2; IntAct=EBI-1056807, EBI-8542977; CC P09958; K9N5Q8: S; Xeno; NbExp=3; IntAct=EBI-1056807, EBI-25474996; CC P09958; P0DTC2: S; Xeno; NbExp=5; IntAct=EBI-1056807, EBI-25474821; CC P09958; Q91QT1: s; Xeno; NbExp=2; IntAct=EBI-1056807, EBI-25690542; CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane CC {ECO:0000269|PubMed:11331585, ECO:0000269|PubMed:11799113, CC ECO:0000269|PubMed:8846780, ECO:0000269|PubMed:9130696, CC ECO:0000269|PubMed:9412467}; Single-pass type I membrane protein CC {ECO:0000305}. Cell membrane {ECO:0000269|PubMed:11799113, CC ECO:0000269|PubMed:9130696, ECO:0000269|PubMed:9412467}; Single-pass CC type I membrane protein {ECO:0000305}. Secreted CC {ECO:0000305|PubMed:11799113}. Endosome membrane CC {ECO:0000269|PubMed:9412467}; Single-pass type I membrane protein CC {ECO:0000305}. Note=Shuttles between the trans-Golgi network and the CC cell surface (PubMed:9412467, PubMed:11799113). Propeptide cleavage is CC a prerequisite for exit of furin molecules out of the endoplasmic CC reticulum (ER). A second cleavage within the propeptide occurs in the CC trans Golgi network (TGN), followed by the release of the propeptide CC and the activation of furin (PubMed:11799113). CC {ECO:0000269|PubMed:11799113, ECO:0000269|PubMed:9412467}. CC -!- TISSUE SPECIFICITY: Seems to be expressed ubiquitously. CC {ECO:0000269|PubMed:1713771}. CC -!- DOMAIN: Contains a cytoplasmic domain responsible for its TGN CC localization and recycling from the cell surface. CC {ECO:0000269|PubMed:8846780}. CC -!- PTM: The inhibition peptide, which plays the role of an intramolecular CC chaperone, is autocatalytically removed in the endoplasmic reticulum CC (ER) and remains non-covalently bound to furin as a potent CC autoinhibitor. Following transport to the trans Golgi, a second CC cleavage within the inhibition propeptide results in propeptide CC dissociation and furin activation. {ECO:0000269|PubMed:1629222, CC ECO:0000269|PubMed:9130696}. CC -!- PTM: Phosphorylation is required for TGN localization of the CC endoprotease. In vivo, exists as di-, mono- and non-phosphorylated CC forms. {ECO:0000269|PubMed:8846780}. CC -!- SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40646/FURIN"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X17094; CAA34948.1; -; mRNA. DR EMBL; BC012181; AAH12181.1; -; mRNA. DR EMBL; X15723; CAA33745.1; -; Genomic_DNA. DR EMBL; X04329; CAA27860.1; -; Genomic_DNA. DR CCDS; CCDS10364.1; -. DR PIR; A39552; KXHUF. DR RefSeq; NP_001276752.1; NM_001289823.1. DR RefSeq; NP_001276753.1; NM_001289824.1. DR RefSeq; NP_002560.1; NM_002569.3. DR PDB; 4OMC; X-ray; 2.30 A; A/B/C/D/E/F=108-574. DR PDB; 4OMD; X-ray; 2.70 A; A/B/C/D/E/F=108-574. DR PDB; 4RYD; X-ray; 2.15 A; A/B/C/D/E/F=108-574. DR PDB; 4Z2A; X-ray; 1.89 A; A=110-574. DR PDB; 5JMO; X-ray; 2.00 A; A/B=108-574. DR PDB; 5JXG; X-ray; 1.80 A; A=108-574. DR PDB; 5JXH; X-ray; 2.00 A; A=108-574. DR PDB; 5JXI; X-ray; 2.00 A; A=108-574. DR PDB; 5JXJ; X-ray; 2.00 A; A=108-574. DR PDB; 5MIM; X-ray; 1.90 A; A=108-574. DR PDB; 6A8Y; NMR; -; A=64-89. DR PDB; 6EQV; X-ray; 1.90 A; A=108-574. DR PDB; 6EQW; X-ray; 1.99 A; A=108-574. DR PDB; 6EQX; X-ray; 1.99 A; A=108-567. DR PDB; 6HLB; X-ray; 2.00 A; A=108-574. DR PDB; 6HLD; X-ray; 2.10 A; A=108-574. DR PDB; 6HLE; X-ray; 1.99 A; A=108-574. DR PDB; 6HZA; X-ray; 1.90 A; A=108-574. DR PDB; 6HZB; X-ray; 1.90 A; A=108-574. DR PDB; 6HZC; X-ray; 1.90 A; A=108-574. DR PDB; 6HZD; X-ray; 1.90 A; A=108-574. DR PDB; 6YD2; X-ray; 1.80 A; A=108-574. DR PDB; 6YD3; X-ray; 2.00 A; A=108-574. DR PDB; 6YD4; X-ray; 1.70 A; A=108-574. DR PDB; 6YD7; X-ray; 1.80 A; A=108-574. DR PDB; 7LCU; X-ray; 1.24 A; A=108-574. DR PDB; 7O1U; X-ray; 1.70 A; A=108-574. DR PDB; 7O1W; X-ray; 1.80 A; A=108-574. DR PDB; 7O1Y; X-ray; 1.70 A; A=108-574. DR PDB; 7O20; X-ray; 1.80 A; A=108-574. DR PDB; 7O22; X-ray; 1.80 A; A=108-574. DR PDB; 7QXY; X-ray; 1.48 A; A=108-574. DR PDB; 7QXZ; X-ray; 1.80 A; A=108-574. DR PDB; 7QY0; X-ray; 1.54 A; A=108-574. DR PDB; 7QY1; X-ray; 1.45 A; A=108-574. DR PDB; 7QY2; X-ray; 1.55 A; A=108-574. DR PDB; 8B4V; X-ray; 1.60 A; A=108-574. DR PDB; 8B4W; X-ray; 1.60 A; A=108-574. DR PDB; 8B4X; X-ray; 1.60 A; A=108-574. DR PDBsum; 4OMC; -. DR PDBsum; 4OMD; -. DR PDBsum; 4RYD; -. DR PDBsum; 4Z2A; -. DR PDBsum; 5JMO; -. DR PDBsum; 5JXG; -. DR PDBsum; 5JXH; -. DR PDBsum; 5JXI; -. DR PDBsum; 5JXJ; -. DR PDBsum; 5MIM; -. DR PDBsum; 6A8Y; -. DR PDBsum; 6EQV; -. DR PDBsum; 6EQW; -. DR PDBsum; 6EQX; -. DR PDBsum; 6HLB; -. DR PDBsum; 6HLD; -. DR PDBsum; 6HLE; -. DR PDBsum; 6HZA; -. DR PDBsum; 6HZB; -. DR PDBsum; 6HZC; -. DR PDBsum; 6HZD; -. DR PDBsum; 6YD2; -. DR PDBsum; 6YD3; -. DR PDBsum; 6YD4; -. DR PDBsum; 6YD7; -. DR PDBsum; 7LCU; -. DR PDBsum; 7O1U; -. DR PDBsum; 7O1W; -. DR PDBsum; 7O1Y; -. DR PDBsum; 7O20; -. DR PDBsum; 7O22; -. DR PDBsum; 7QXY; -. DR PDBsum; 7QXZ; -. DR PDBsum; 7QY0; -. DR PDBsum; 7QY1; -. DR PDBsum; 7QY2; -. DR PDBsum; 8B4V; -. DR PDBsum; 8B4W; -. DR PDBsum; 8B4X; -. DR AlphaFoldDB; P09958; -. DR SMR; P09958; -. DR BioGRID; 111082; 250. DR CORUM; P09958; -. DR DIP; DIP-29904N; -. DR ELM; P09958; -. DR IntAct; P09958; 25. DR MINT; P09958; -. DR STRING; 9606.ENSP00000483552; -. DR BindingDB; P09958; -. DR ChEMBL; CHEMBL2611; -. DR DrugBank; DB03600; Capric acid. DR GuidetoPHARMACOLOGY; 2366; -. DR MEROPS; S08.071; -. DR TCDB; 1.A.9.1.24; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family. DR TCDB; 9.B.355.2.1; the dentilisin (dentilisin) family. DR GlyCosmos; P09958; 3 sites, No reported glycans. DR GlyGen; P09958; 3 sites. DR iPTMnet; P09958; -. DR PhosphoSitePlus; P09958; -. DR SwissPalm; P09958; -. DR BioMuta; FURIN; -. DR DMDM; 120611; -. DR OGP; P09958; -. DR EPD; P09958; -. DR jPOST; P09958; -. DR MassIVE; P09958; -. DR MaxQB; P09958; -. DR PaxDb; 9606-ENSP00000483552; -. DR PeptideAtlas; P09958; -. DR ProteomicsDB; 52283; -. DR Pumba; P09958; -. DR ABCD; P09958; 1 sequenced antibody. DR Antibodypedia; 4013; 496 antibodies from 39 providers. DR DNASU; 5045; -. DR Ensembl; ENST00000268171.8; ENSP00000268171.2; ENSG00000140564.13. DR Ensembl; ENST00000610579.4; ENSP00000484952.1; ENSG00000140564.13. DR Ensembl; ENST00000618099.4; ENSP00000483552.1; ENSG00000140564.13. DR Ensembl; ENST00000680053.1; ENSP00000506143.1; ENSG00000140564.13. DR GeneID; 5045; -. DR KEGG; hsa:5045; -. DR MANE-Select; ENST00000268171.8; ENSP00000268171.2; NM_002569.4; NP_002560.1. DR UCSC; uc002bpu.2; human. DR AGR; HGNC:8568; -. DR CTD; 5045; -. DR DisGeNET; 5045; -. DR GeneCards; FURIN; -. DR HGNC; HGNC:8568; FURIN. DR HPA; ENSG00000140564; Tissue enhanced (liver, salivary gland). DR MIM; 136950; gene. DR neXtProt; NX_P09958; -. DR OpenTargets; ENSG00000140564; -. DR PharmGKB; PA32894; -. DR VEuPathDB; HostDB:ENSG00000140564; -. DR eggNOG; KOG3525; Eukaryota. DR GeneTree; ENSGT00940000157220; -. DR HOGENOM; CLU_002976_4_0_1; -. DR InParanoid; P09958; -. DR OMA; FREWAFM; -. DR OrthoDB; 5474719at2759; -. DR PhylomeDB; P09958; -. DR TreeFam; TF314277; -. DR BRENDA; 3.4.21.75; 2681. DR PathwayCommons; P09958; -. DR Reactome; R-HSA-1181150; Signaling by NODAL. DR Reactome; R-HSA-1442490; Collagen degradation. DR Reactome; R-HSA-1566948; Elastic fibre formation. DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases. DR Reactome; R-HSA-159782; Removal of aminoterminal propeptides from gamma-carboxylated proteins. DR Reactome; R-HSA-167060; NGF processing. DR Reactome; R-HSA-171286; Synthesis and processing of ENV and VPU. DR Reactome; R-HSA-186797; Signaling by PDGF. DR Reactome; R-HSA-1912420; Pre-NOTCH Processing in Golgi. DR Reactome; R-HSA-2173789; TGF-beta receptor signaling activates SMADs. DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription. DR Reactome; R-HSA-5210891; Uptake and function of anthrax toxins. DR Reactome; R-HSA-6809371; Formation of the cornified envelope. DR Reactome; R-HSA-8963889; Assembly of active LPL and LIPC lipase complexes. DR Reactome; R-HSA-9662834; CD163 mediating an anti-inflammatory response. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR Reactome; R-HSA-9694614; Attachment and Entry. DR Reactome; R-HSA-9733458; Induction of Cell-Cell Fusion. DR Reactome; R-HSA-977225; Amyloid fiber formation. DR SignaLink; P09958; -. DR SIGNOR; P09958; -. DR BioGRID-ORCS; 5045; 166 hits in 1183 CRISPR screens. DR ChiTaRS; FURIN; human. DR GeneWiki; Furin; -. DR GenomeRNAi; 5045; -. DR Pharos; P09958; Tchem. DR PRO; PR:P09958; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; P09958; Protein. DR Bgee; ENSG00000140564; Expressed in right lobe of liver and 192 other cell types or tissues. DR ExpressionAtlas; P09958; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; IGI:BHF-UCL. DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0000139; C:Golgi membrane; IMP:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005802; C:trans-Golgi network; IDA:BHF-UCL. DR GO; GO:0030140; C:trans-Golgi network transport vesicle; IDA:MGI. DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB. DR GO; GO:1904399; F:heparan sulfate binding; IDA:UniProtKB. DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0048406; F:nerve growth factor binding; IDA:BHF-UCL. DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB. DR GO; GO:0042277; F:peptide binding; IDA:BHF-UCL. DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL. DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:BHF-UCL. DR GO; GO:0008236; F:serine-type peptidase activity; IDA:UniProt. DR GO; GO:1990000; P:amyloid fibril formation; TAS:Reactome. DR GO; GO:0001825; P:blastocyst formation; IEA:Ensembl. DR GO; GO:0030574; P:collagen catabolic process; TAS:Reactome. DR GO; GO:0140447; P:cytokine precursor processing; IDA:UniProtKB. DR GO; GO:0090472; P:dibasic protein processing; IMP:UniProtKB. DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome. DR GO; GO:0030198; P:extracellular matrix organization; TAS:Reactome. DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; TAS:Reactome. DR GO; GO:0032804; P:negative regulation of low-density lipoprotein particle receptor catabolic process; IDA:HGNC-UCL. DR GO; GO:0032911; P:negative regulation of transforming growth factor beta1 production; IMP:BHF-UCL. DR GO; GO:0032902; P:nerve growth factor production; IDA:BHF-UCL. DR GO; GO:0043043; P:peptide biosynthetic process; IDA:BHF-UCL. DR GO; GO:0016486; P:peptide hormone processing; IDA:BHF-UCL. DR GO; GO:0034369; P:plasma lipoprotein particle remodeling; TAS:Reactome. DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; IC:BHF-UCL. DR GO; GO:0046598; P:positive regulation of viral entry into host cell; IDA:UniProtKB. DR GO; GO:0051604; P:protein maturation; IDA:UniProt. DR GO; GO:0016485; P:protein processing; IDA:UniProtKB. DR GO; GO:0032374; P:regulation of cholesterol transport; IEA:Ensembl. DR GO; GO:0052548; P:regulation of endopeptidase activity; IDA:BHF-UCL. DR GO; GO:0042176; P:regulation of protein catabolic process; IMP:BHF-UCL. DR GO; GO:0009966; P:regulation of signal transduction; IEA:Ensembl. DR GO; GO:0032940; P:secretion by cell; IDA:BHF-UCL. DR GO; GO:0006465; P:signal peptide processing; IDA:HGNC-UCL. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome. DR GO; GO:0019058; P:viral life cycle; IEP:BHF-UCL. DR GO; GO:0019082; P:viral protein processing; TAS:Reactome. DR GO; GO:0019081; P:viral translation; TAS:UniProt. DR GO; GO:0031638; P:zymogen activation; IMP:UniProtKB. DR CDD; cd00064; FU; 2. DR CDD; cd04059; Peptidases_S8_Protein_convertases_Kexins_Furin-like; 1. DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1. DR Gene3D; 3.30.70.850; Peptidase S8, pro-domain; 1. DR Gene3D; 3.40.50.200; Peptidase S8/S53 domain; 1. DR InterPro; IPR006212; Furin_repeat. DR InterPro; IPR008979; Galactose-bd-like_sf. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR034182; Kexin/furin. DR InterPro; IPR002884; P_dom. DR InterPro; IPR000209; Peptidase_S8/S53_dom. DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf. DR InterPro; IPR023827; Peptidase_S8_Asp-AS. DR InterPro; IPR022398; Peptidase_S8_His-AS. DR InterPro; IPR023828; Peptidase_S8_Ser-AS. DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel. DR InterPro; IPR032815; S8_pro-domain. DR InterPro; IPR038466; S8_pro-domain_sf. DR PANTHER; PTHR42884:SF1; FURIN; 1. DR PANTHER; PTHR42884; PROPROTEIN CONVERTASE SUBTILISIN/KEXIN-RELATED; 1. DR Pfam; PF01483; P_proprotein; 1. DR Pfam; PF00082; Peptidase_S8; 1. DR Pfam; PF16470; S8_pro-domain; 1. DR PRINTS; PR00723; SUBTILISIN. DR SMART; SM00261; FU; 2. DR SUPFAM; SSF49785; Galactose-binding domain-like; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF54897; Protease propeptides/inhibitors; 1. DR SUPFAM; SSF52743; Subtilisin-like; 1. DR PROSITE; PS51829; P_HOMO_B; 1. DR PROSITE; PS51892; SUBTILASE; 1. DR PROSITE; PS00136; SUBTILASE_ASP; 1. DR PROSITE; PS00137; SUBTILASE_HIS; 1. DR PROSITE; PS00138; SUBTILASE_SER; 1. DR Genevisible; P09958; HS. PE 1: Evidence at protein level; KW 3D-structure; Autocatalytic cleavage; Calcium; Cell membrane; KW Cleavage on pair of basic residues; Disulfide bond; Endosome; Glycoprotein; KW Golgi apparatus; Heparin-binding; Host-virus interaction; Hydrolase; KW Membrane; Metal-binding; Phosphoprotein; Protease; Reference proteome; KW Repeat; Secreted; Serine protease; Signal; Transmembrane; KW Transmembrane helix; Zymogen. FT SIGNAL 1..26 FT /evidence="ECO:0000255" FT PROPEP 27..107 FT /note="Inhibition peptide" FT /evidence="ECO:0000269|PubMed:9130696" FT /id="PRO_0000027028" FT CHAIN 108..794 FT /note="Furin" FT /id="PRO_0000027029" FT TOPO_DOM 108..715 FT /note="Lumenal" FT /evidence="ECO:0000305" FT TRANSMEM 716..738 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 739..794 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT DOMAIN 121..435 FT /note="Peptidase S8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240" FT DOMAIN 444..576 FT /note="P/Homo B" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01173" FT REPEAT 577..620 FT /note="FU 1" FT /evidence="ECO:0000255" FT REPEAT 638..681 FT /note="FU 2" FT /evidence="ECO:0000255" FT REGION 162..183 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 673..696 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 759..762 FT /note="Cell surface signal" FT /evidence="ECO:0000303|PubMed:9412467" FT REGION 767..794 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 498..500 FT /note="Cell attachment site" FT /evidence="ECO:0000255" FT MOTIF 773..779 FT /note="Trans Golgi network signal" FT /evidence="ECO:0000269|PubMed:8846780" FT COMPBIAS 673..687 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 153 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240" FT ACT_SITE 194 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240" FT ACT_SITE 368 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240" FT BINDING 115 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 154 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:24666235, FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 162 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 174 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 179 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 181 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 191..192 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:24666235, FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 205 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 208 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 210 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 212 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 236 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:24666235, FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 253..258 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:24666235, FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 258 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 264 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:24666235, FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 292..295 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:24666235, FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 301 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 306 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:24666235, FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 308 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:24666235, FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 331 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT BINDING 368 FT /ligand="substrate" FT /evidence="ECO:0000305|PubMed:24666235, FT ECO:0000305|PubMed:25974265, ECO:0007744|PDB:4OMC, FT ECO:0007744|PDB:4OMD, ECO:0007744|PDB:4RYD" FT SITE 75..76 FT /note="Cleavage, second; by autolysis" FT /evidence="ECO:0000269|PubMed:9130696" FT SITE 107..108 FT /note="Cleavage, first; by autolysis" FT /evidence="ECO:0000269|PubMed:1629222, FT ECO:0000269|PubMed:9130696" FT MOD_RES 773 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:8846780" FT MOD_RES 775 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:8846780" FT CARBOHYD 387 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 440 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 553 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 211..360 FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265" FT DISULFID 303..333 FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265" FT DISULFID 450..474 FT /evidence="ECO:0000269|PubMed:24666235, FT ECO:0000269|PubMed:25974265" FT VARIANT 43 FT /note="A -> V (in dbSNP:rs16944971)" FT /evidence="ECO:0000269|PubMed:32867305" FT /id="VAR_051821" FT VARIANT 146 FT /note="G -> S" FT /evidence="ECO:0000269|PubMed:32867305" FT /id="VAR_084542" FT VARIANT 298 FT /note="R -> Q" FT /evidence="ECO:0000269|PubMed:32867305" FT /id="VAR_084543" FT VARIANT 547 FT /note="W -> R (in cell line LoVo; does not undergo FT autocatalytic activation and is not transported to the FT Golgi apparatus)" FT /evidence="ECO:0000269|PubMed:7592877" FT /id="VAR_055343" FT VARIANT 636 FT /note="I -> V" FT /evidence="ECO:0000269|PubMed:32867305" FT /id="VAR_084544" FT MUTAGEN 72 FT /note="V->R: Loss of catalytic activity and propeptide FT second cleavage and removal. Abnormal accumulation in the FT early secretory pathway." FT /evidence="ECO:0000269|PubMed:11799113" FT MUTAGEN 75 FT /note="R->A: Loss of catalytic activity and, propeptide FT second cleavage and removal. Normal trafficking to the FT Golgi." FT /evidence="ECO:0000269|PubMed:11799113" FT MUTAGEN 153 FT /note="D->N: Loss of catalytic activity and propeptide FT first cleavage. Abnormal accumulation in the early FT secretory pathway." FT /evidence="ECO:0000269|PubMed:11799113, FT ECO:0000269|PubMed:9130696" FT MUTAGEN 773..775 FT /note="SDS->DDD: Phosphomimetic mutant. Localization in FT early endosome is increased." FT /evidence="ECO:0000269|PubMed:8846780" FT MUTAGEN 773 FT /note="S->A: Slight reduction in phosphorylation. Loss of FT phosphorylation and abnormal accumulation in the early FT secretory pathway; when associated with A-775." FT /evidence="ECO:0000269|PubMed:8846780" FT MUTAGEN 775 FT /note="S->A: Slight reduction in phosphorylation. Loss of FT phosphorylation and abnormal accumulation in the early FT secretory pathway; when associated with A-773." FT /evidence="ECO:0000269|PubMed:8846780" FT HELIX 66..68 FT /evidence="ECO:0007829|PDB:6A8Y" FT HELIX 73..77 FT /evidence="ECO:0007829|PDB:6A8Y" FT STRAND 78..80 FT /evidence="ECO:0007829|PDB:6A8Y" FT TURN 82..84 FT /evidence="ECO:0007829|PDB:6A8Y" FT HELIX 85..88 FT /evidence="ECO:0007829|PDB:6A8Y" FT HELIX 118..120 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 122..125 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 127..129 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 134..139 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 148..154 FT /evidence="ECO:0007829|PDB:7LCU" FT TURN 161..163 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 164..166 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 169..171 FT /evidence="ECO:0007829|PDB:7LCU" FT TURN 175..178 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 191..193 FT /evidence="ECO:0007829|PDB:6YD4" FT HELIX 194..203 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 206..211 FT /evidence="ECO:0007829|PDB:7LCU" FT TURN 215..218 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 219..225 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 227..229 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 233..240 FT /evidence="ECO:0007829|PDB:7LCU" FT TURN 244..246 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 249..252 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 259..261 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 268..280 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 282..284 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 288..292 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 297..299 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 303..305 FT /evidence="ECO:0007829|PDB:7LCU" FT TURN 307..310 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 314..320 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 338..341 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 351..355 FT /evidence="ECO:0007829|PDB:7LCU" FT TURN 356..358 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 359..364 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 367..369 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 370..384 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 390..400 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 419..421 FT /evidence="ECO:0007829|PDB:7LCU" FT TURN 422..424 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 431..438 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 448..453 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 464..471 FT /evidence="ECO:0007829|PDB:7LCU" FT TURN 473..476 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 482..496 FT /evidence="ECO:0007829|PDB:7LCU" FT HELIX 498..500 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 501..506 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 512..516 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 528..535 FT /evidence="ECO:0007829|PDB:7LCU" FT TURN 537..540 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 545..553 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 555..557 FT /evidence="ECO:0007829|PDB:7LCU" FT STRAND 561..573 FT /evidence="ECO:0007829|PDB:7LCU" SQ SEQUENCE 794 AA; 86678 MW; 10C44DD5892EF85D CRC64; MELRPWLLWV VAATGTLVLL AADAQGQKVF TNTWAVRIPG GPAVANSVAR KHGFLNLGQI FGDYYHFWHR GVTKRSLSPH RPRHSRLQRE PQVQWLEQQV AKRRTKRDVY QEPTDPKFPQ QWYLSGVTQR DLNVKAAWAQ GYTGHGIVVS ILDDGIEKNH PDLAGNYDPG ASFDVNDQDP DPQPRYTQMN DNRHGTRCAG EVAAVANNGV CGVGVAYNAR IGGVRMLDGE VTDAVEARSL GLNPNHIHIY SASWGPEDDG KTVDGPARLA EEAFFRGVSQ GRGGLGSIFV WASGNGGREH DSCNCDGYTN SIYTLSISSA TQFGNVPWYS EACSSTLATT YSSGNQNEKQ IVTTDLRQKC TESHTGTSAS APLAAGIIAL TLEANKNLTW RDMQHLVVQT SKPAHLNAND WATNGVGRKV SHSYGYGLLD AGAMVALAQN WTTVAPQRKC IIDILTEPKD IGKRLEVRKT VTACLGEPNH ITRLEHAQAR LTLSYNRRGD LAIHLVSPMG TRSTLLAARP HDYSADGFND WAFMTTHSWD EDPSGEWVLE IENTSEANNY GTLTKFTLVL YGTAPEGLPV PPESSGCKTL TSSQACVVCE EGFSLHQKSC VQHCPPGFAP QVLDTHYSTE NDVETIRASV CAPCHASCAT CQGPALTDCL SCPSHASLDP VEQTCSRQSQ SSRESPPQQQ PPRLPPEVEA GQRLRAGLLP SHLPEVVAGL SCAFIVLVFV TVFLVLQLRS GFSFRGVKVY TMDRGLISYK GLPPEAWQEE CPSDSEEDEG RGERTAFIKD QSAL //